Surgical options for rectal cancer that has spread to the liver

순서

1. UpToDate 2020.02.20

2. Goldman-Cecil Internal Medicine 26th edition

3. Harrison's Internal Medicine 20th edition

4. NCCN guideline 2017, 2018, 2020

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Management of synchronous hepatic metastases — The surgical approach to resecting synchronous CRC liver metastases is more complex. Patients have the option of undergoing simultaneous resection of the primary tumor and the metastases or a staged resection, which can be colorectal first (classic) or liver first (reverse approach). Systematic reviews and meta-analyses show no difference in outcomes regardless of which approach is taken. Thus, the decision to perform a staged or simultaneous resection, and whether to do a classic or reverse approach for a staged resection should be individualized to each patient. In general, simultaneous resection of the primary tumor and the hepatic metastases is clearly preferable from the patient's perspective.

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Timing and sequence of surgical therapy — Treatment of patients with synchronous CRC liver metastases is often multidisciplinary and multimodal, involving chemotherapy, sometimes chemoradiotherapy (for a patient with a rectal primary), surgery, and possibly other forms of locoregional therapy. There is no standard approach to these patients. In particular, the role of neoadjuvant chemotherapy, particularly for those with initially resectable hepatic metastases, is controversial.

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The timing and sequence of surgical resection of the primary tumor and metastases mostly depend on the acuity of symptoms and disease burden. In general (㉮, ㉯)​

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㉮ Patients who present with symptoms from the primary CRC (eg, bleeding, obstruction, or perforation) should undergo resection of the colorectal primary tumor first. Utilizing the liver-first approach increases the risk of developing complications related to the primary CRC.

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㉯ Patients who are asymptomatic from the primary CRC may undergo a simultaneous or staged resection, depending on the extent of their liver involvement: (㉠, ㉡, ㉢)

㉠ Patients with a colorectal primary lesion in a favorable location (eg, right colon) and limited liver metastases may undergo simultaneous resection.

㉡ Patients with extensive bilobar disease would benefit from the classic (colorectal-first) two-stage approach. R0 resection of such extensive CRC liver metastases often requires an anatomic resection combined with multiple partial hepatectomies. This typically cannot be accomplished in a single operation because of a high risk of liver failure. With the classic approach, at the time of colorectal primary resection, the hepatic metastases on the future liver remnant are resected with partial hepatectomies, leaving tumors behind on the portion of the liver that can be treated with a future anatomic resection. The patient then undergoes embolization of the portal vein on the side with the remaining tumors. After an adequate hypertrophy of the future liver remnant, a formal anatomic resection of the remaining disease can be performed as the second-stage operation.

㉢ However, some patients may benefit from a liver-first two-stage approach. As an example, patients with locally advanced rectal cancer (T4 and/or bulky tumor, or extensive nodal disease) are often treated with intensified preoperative therapy using induction chemotherapy followed by chemoradiotherapy instead of chemoradiotherapy alone. If such patients have synchronous potentially resectable liver metastases, they would be candidates for the reverse (liver-first) two-stage approach to resection: after four months of induction chemotherapy, hepatic resection typically takes place first; colorectal resection then follows in another two to four months upon completion of chemoradiotherapy, with or without two additional months of chemotherapy. Delaying hepatic resection until a simultaneous resection can be carried out (at six to eight months) may worsen chemotherapy-induced liver changes and increase the risk of postoperative liver failure.

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NEOADJUVANT CHEMOTHERAPY

The availability of increasingly effective systemic chemotherapy has prompted interest in preoperative or neoadjuvant systemic chemotherapy prior to liver resection. Initial systemic chemotherapy is often undertaken as a means of assessing the natural history of metastatic disease prior to embarking on metastasectomy (particularly in patients with a synchronous presentation of metastatic disease). However, neoadjuvant systemic chemotherapy also has the potential to convert some patients with initially unresectable large or critically located liver metastases to resectable disease, although the true frequency with which this occurs is probably low. The optimal selection criteria, the specific regimen and duration of neoadjuvant chemotherapy, and the best way in which chemotherapy should be interdigitated with surgery in patients who present with synchronous metastatic disease have not been defined.

The growing number of reports describing liver toxicity and higher rates of perioperative morbidity in patients undergoing resection after receiving oxaliplatin- or irinotecan-based neoadjuvant chemotherapy have somewhat tempered enthusiasm for this approach, particularly in patients with a small number of initially resectable liver metastases.

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For this reason, we suggest the following approach:

● For low-risk (medically fit, four or fewer lesions, metachronous, liver-only site), potentially resectable patients, initial surgery rather than neoadjuvant chemotherapy should be chosen, followed by postoperative chemotherapy.

● For patients who have higher risk, borderline resectable or unresectable disease, neoadjuvant chemotherapy is the preferred approach.

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Regardless of the specific regimen chosen, the duration of neoadjuvant chemotherapy should be limited, radiographic response assessment should be performed at approximately six- to eight-week intervals, and surgery should be undertaken as soon as the metastases become clearly resectable. Liver resection should be delayed at least four weeks after completion of chemotherapy, six to eight weeks if bevacizumab was a component of therapy.

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Locally Directed Treatment of Metastatic Disease

For selected patients with metastatic colorectal cancer, complete resection of hepatic or pulmonary metastases can sometimes provide long-term survival and has become the standard of care. For hepatic metastasectomy, 5-year survival rates are in the 30 to 50% range, but later relapses suggest that 5-year survival may not be an accurate reflection of true cure. In patients initially deemed to have surgically unresectable metastatic disease, preoperative systemic therapy improves response rates. For patients with wild-type RAS disease, for example, cytotoxic chemotherapy with FOLFOX or FOLFIRI in combination with cetuximab or panitumumab offers the best chance for cytoreduction of the metastatic liver disease and successful surgical resection. In the setting of mutant RAS metastatic colorectal cancer, the anti-VEGF antibody bevacizumab combined with chemotherapy provides an objective response rate approaching 70% with successful surgical resection approaching 30%. After patients have recovered from their metastasectomy procedure, which usually takes 4 to 5 weeks, 6 months of adjuvant chemotherapy with FOLFOX is usually recommended.

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Colorectal Cancer

Local disease: Surgical resection of colonic segment containing tumor; preoperative evaluation to assess prognosis and surgical approach includes full colonoscopy, chest films, biochemical liver tests, plasma CEA level, and possible abdominal CT. Resection of isolated hepatic metastases possible in selected cases. Adjuvant radiation therapy to pelvis with concomitant 5FU chemotherapy decreases local recurrence rate of rectal carcinoma (no apparent effect on survival); radiation therapy without benefit on colon tumors; ​preoperative radiation therapy may improve resectability and local control in pts with rectal cancer. Total mesorectal excision is more effective than conventional anteroposterior resection in rectal cancer. Adjuvant chemotherapy (5FU/leucovorin plus oxaliplatin, or FOLFOX plus bevacizumab, or 5FU/leucovorin plus irinotecan, or FOLFIRI) decreases recurrence rate and improves survival of stage C (III); survival benefit from adjuvant therapy is not so clear in stage B (II) tumors; periodic determination of serum CEA level useful to follow therapy and assess recurrence.

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Follow-up after curative resection: Yearly liver tests, complete blood count, follow-up radiologic or colonoscopic evaluation at 1 year—if normal, repeat every 3 years, with routine screening interim (see below); if polyps detected, repeat 1 year after resection.

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Advanced tumor (locally unresectable or metastatic): Systemic chemotherapy (5FU/leucovorin plus oxaliplatin plus bevacizumab), irinotecan usually used in second treatment; antibodies to the epidermal growth factor (EGF) receptor (cetuximab, panitumumab) appear to enhance the effect of chemotherapy but are ineffective in tumors with ras mutations; intraarterial chemotherapy (floxuridine [FUDR]) and/or radiation therapy may palliate symptoms from hepatic metastases. Solitary hepatic metastases may be resected by partial hepatectomy with 25% 5-year survival. The subset of pts with mismatch repair deficiency appear more sensitive to chemotherapy and to immune checkpoint inhibitors.

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1. 2017 Surgical options for rectal cancer that has spread to the liver or lungs (NCCN)

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2. 2018 Surgical options for rectal cancer that has spread to the liver or lungs (NCCN)

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3. 2020 Surgical options for rectal cancer that has spread to the liver or lungs (NCCN)

NCCN Guidelines Version 2020 Rectal Cancer.pdf

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